Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.
Clozapine (1-10 mg/kg s.c.) produces a selective increase in dopamine release in rat prefrontal cortex which is, in large part (approximately 50%), mediated via activation of 5-HT1A receptors. Clozapine is a moderately potent, partial 5-HT1A receptor agonist and activation of 5-HT1A receptors may contribute to its efficacy against negative symptoms and reduced extrapyramidal side effect liability. Agonist affinity for 5-HT1A receptors could thus be a desirable feature in the design of new antipsychotics.
Rollema
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Pfizer Inc., Department of Neuroscience, Groton, CT 06340, USA. hans_rollema@groton.pfizer.com
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Schmidt
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Zorn
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D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D003024:Clozapine; D004298:Dopamine